Neuromuscular disease caused by qualitative or quantitative defects of plectin

Summary

Neuromuscular disease caused by qualitative or quantitative defects of plectin (MONDO:0016198) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuromuscular disease caused by qualitative or quantitative defects of plectin
Mondo ID	MONDO:0016198
Orphanet	209196
UMLS	C5680835
MedGen	1842345
GARD	0020437
Is cancer (heuristic)	no

Also known as: PLEC-related muscular dystrophy-epidermolysis bullosa simplex spectrum disorder · qualitative or quantitative defects of plectin

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › neuromuscular disease caused by qualitative or quantitative defects of plectin

Related subtypes (18): sarcoglycanopathy, neuromuscular disease caused by qualitative or quantitative defects of dysferlin, caveolinopathy, neuromuscular disease caused by qualitative or quantitative defects of dystrophin, neuromuscular disease caused by qualitative or quantitative defects of perlecan, neuromuscular disease caused by qualitative or quantitative defects of TRIM32, neuromuscular disease caused by qualitative or quantitative defects of myofibrillar proteins, neuromuscular disease caused by qualitative or quantitative defects of titin, neuromuscular disease caused by qualitative or quantitative defects of telethonin, neuromuscular disease caused by qualitative or quantitative defects of alpha-actin, neuromuscular disease caused by qualitative or quantitative defects of nebulin, neuromuscular disease caused by qualitative or quantitative defects of beta-myosin heavy chain (MYH7), neuromuscular disease caused by qualitative or quantitative defects of selenoprotein N1, neuromuscular disease caused by qualitative or quantitative defects of protein SERCA1, neuromuscular disease caused by qualitative or quantitative defects of tropomyosin, neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan, alpha-actinopathy, collagen 6-related myopathy

Subtypes (2): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2Q

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2500919	NM_201384.3(PLEC):c.1210G>T (p.Glu404Ter)	PLEC	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLEC	Orphanet:1114	Aplasia cutis congenita
PLEC	Orphanet:158684	Epidermolysis bullosa simplex with pyloric atresia
PLEC	Orphanet:254361	Plectin-related limb-girdle muscular dystrophy R17
PLEC	Orphanet:257	Epidermolysis bullosa simplex with muscular dystrophy
PLEC	Orphanet:79401	PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLEC	HGNC:9069	ENSG00000178209	Q15149	Plectin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLEC	Plectin	Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLEC	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLEC	283	ubiquitous	marker	sural nerve, hindlimb stylopod muscle, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLEC	3,529

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLEC	Q15149	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Type I hemidesmosome assembly	1	1038.2×	0.002	PLEC
Caspase-mediated cleavage of cytoskeletal proteins	1	951.7×	0.002	PLEC
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.005	PLEC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein-containing complex organization	1	16852.0×	9e-04	PLEC
actomyosin contractile ring assembly actin filament organization	1	16852.0×	9e-04	PLEC
skeletal myofibril assembly	1	8426.0×	0.001	PLEC
leukocyte migration involved in immune response	1	5617.3×	0.001	PLEC
cellular response to hydrostatic pressure	1	5617.3×	0.001	PLEC
tight junction organization	1	3370.4×	0.002	PLEC
hemidesmosome assembly	1	2407.4×	0.002	PLEC
keratinocyte development	1	1532.0×	0.002	PLEC
peripheral nervous system myelin maintenance	1	1532.0×	0.002	PLEC
cellular response to fluid shear stress	1	1296.3×	0.002	PLEC
T cell chemotaxis	1	1123.5×	0.002	PLEC
regulation of vascular permeability	1	1123.5×	0.002	PLEC
intermediate filament cytoskeleton organization	1	936.2×	0.002	PLEC
fibroblast migration	1	842.6×	0.002	PLEC
respiratory electron transport chain	1	842.6×	0.002	PLEC
myoblast differentiation	1	842.6×	0.002	PLEC
transmission of nerve impulse	1	648.1×	0.003	PLEC
cardiac muscle cell development	1	624.1×	0.003	PLEC
nucleus organization	1	561.7×	0.003	PLEC
skeletal muscle fiber development	1	543.6×	0.003	PLEC
adherens junction organization	1	510.7×	0.003	PLEC
response to food	1	495.6×	0.003	PLEC
establishment of skin barrier	1	455.5×	0.003	PLEC
sarcomere organization	1	383.0×	0.003	PLEC
intermediate filament organization	1	240.7×	0.005	PLEC
wound healing	1	227.7×	0.005	PLEC
cellular response to mechanical stimulus	1	216.1×	0.005	PLEC
cell morphogenesis	1	157.5×	0.007	PLEC
mitochondrion organization	1	151.8×	0.007	PLEC
multicellular organism growth	1	137.0×	0.008	PLEC

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLEC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PLEC	12	Binding:12

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PLEC

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PLEC	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.